Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes

The bacterial pathogen Helicobacter pylori commonly colonizes the human gastric mucosa during early childhood and persists throughout life. The organism has evolved multiple mechanisms for evading clearance by the immune system and, despite inducing inflammation in the stomach, the majority of infections are asymptomatic. H. pylori is the leading cause of peptic ulcer disease and gastric cancer. However, disease outcomes are related to the pattern and severity of chronic inflammation in the gastric mucosa, which in turn is influenced by both bacterial and host factors. Despite over 2 decades of intensive research, there remains an incomplete understanding of the circumstances leading to disease development, due to the fascinating complexity of the host-pathogen interactions. There is accumulating data concerning the virulence factors associated with increased risk of disease, and the majority of these have pro-inflammatory activities. Despite this, only a small proportion of those infected with virulent strains develop disease. Several H. pylori virulence factors have multiple effects on different cell types, including the induction of pro- and anti-inflammatory, immune stimulatory, and immune modulatory responses. The expression of multiple virulence factors is also often linked, making it difficult to assess the meaning of their effects in isolation. Overall, H. pylori is thought to usually modulate inflammation and limit acute damage to the mucosa, enabling the bacteria to persist. If this delicate balance is disturbed, disease may then develop

Evidence for symmetric chromosomal inversions around the replication origin in bacteria.

BackgroundWhole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species.ResultsBy comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well.ConclusionsThe most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution

Sequential Symbolic Regression with Genetic Programming

This chapter describes the Sequential Symbolic Regression (SSR) method, a new strategy for function approximation in symbolic regression. The SSR method is inspired by the sequential covering strategy from machine learning, but instead of sequentially reducing the size of the problem being solved, it sequentially transforms the original problem into potentially simpler problems. This transformation is performed according to the semantic distances between the desired and obtained outputs and a geometric semantic operator. The rationale behind SSR is that, after generating a suboptimal function f via symbolic regression, the output errors can be approximated by another function in a subsequent iteration. The method was tested in eight polynomial functions, and compared with canonical genetic programming (GP) and geometric semantic genetic programming (SGP). Results showed that SSR significantly outperforms SGP and presents no statistical difference to GP. More importantly, they show the potential of the proposed strategy: an effective way of applying geometric semantic operators to combine different (partial) solutions, avoiding the exponential growth problem arising from the use of these operators

Ivan Goncharov and the Imperial Horizons of The Frigate Pallada

The article was submitted on 07.12.2018.Review of: Bojanowska, E. M. (2018). A World of Empires: The Russian Voyage of the Frigate Pallada. Cambridge, Mass.; L., The Belknap Press; Harvard Univ. Press. 373 + VIII р. This review examines Edyta M. Bojanowska’s new book on Ivan Goncharov’s voyage to Japan and his subsequent travelogue, The Frigate Pallada. In 1852, Goncharov set sail for Japan from St Petersburg in the hope of opening up the reclusive Asian nation for Russian trade. Along the way, he visited London, the Cape colony in South Africa, and numerous ports in Southeast Asia. After visiting China, Japan, and Korea, he landed in Ayan, from whence he travelled back to the imperial capital over land. The account he wrote about his experiences became an instant classic, although the lack of good translations means that it is virtually unknown in the English-speaking world. In her work, Bojanowska examines both The Frigate Pallada as a text and the history of Russia’s expedition to Japan. Strongly criticising the Soviet philological tradition which saw Goncharov’s work as an anti-colonial text, she argues that the famous Russian writer sought to justify the expansion of Russian and other European empires in Africa, Asia, and Siberia. Nonetheless, Goncharov’s book reflects peculiarly Russian traditions of understanding empire and colonialism: equally, she posits, his work does not (and cannot) present a cohesive system of thought, but a ‘kaleidoscopic’ series of impressions that sometimes contradict The Frigate Pallada’s general themes.В рецензии рассматривается новая книга Эдиты М. Божановской о путешествии Ивана Гончарова в Японию и его травелоге «Фрегат Паллада». В 1852 г. Гончаров отплыл в Японию из Санкт-Петербурга в надежде открыть закрытую страну для российской торговли. По пути он посетил Лондон, Капскую колонию в Южной Африке и многочисленные порты Юго-Восточной Азии. После посещения Китая, Японии и Кореи он высадился в селе Аян, откуда отправился в столицу империи по суше. Свои впечатления Гончаров описал в ставшем впоследствии классическим труде. Однако отсутствие качественных переводов на английский привело к тому, что эта книга была практически не известна в англоговорящем мире. В своей работе Божановска рассматривает «Фрегат Паллада» как текст и как историю российской экспедиции в Японию. Она критикует советскую филологическую традицию, воспринимавшую работу Гончарова как антиколониальный текст. Божановска полагает, что знаменитый русский писатель старался оправдать экспансию России и других европейских стран в Африку, Азию и Сибирь. Тем не менее, книга Гончарова отражает специфические русские традиции понимания империи и колониализма. В то же время автор заявляет, что книга Гончарова не представляет (и не может представлять) связной системы мысли, а является «калейдоскопической» серией впечатлений, которая иногда противоречит главным идеям этого труда.The completion of this review was supported by the Russian Science Fund (RNF), project no. 18–18–00216

MRI and Neuropsychological Correlates of Carbon Monoxide Exposure: A Case Report

A 45-year-old woman experienced long-term, chronic exposure to carbon monoxide in the restaurant kitchen where she was employed as a cook. After returning to the restaurant after 5 days off work, she noticed that her symptoms returned immediately; she then aired out the room and called the gas company. Approximately 6 hr after a leak was detected, the patient went to the hospital, where her carboxyhemoglobin was found to be within normal limits and results of a neurologic examination were described as normal. Based on her symptoms, the patient believed she had been exposed to CO for at least 1 year before the leak was discovered. Initially, she experienced flu-like symptoms, which eventually resolved. At the time of her first neuropsychological evaluation (17 months after the exposure was identified), her persisting complaints included difficulties in reading, writing, speaking and word retrieval. The test results were consistent with secondary frontal lobe dysfunction associated with subcortical disorders such as those seen after CO exposure. Results of a subsequent neuropsychological examination (29 months postexposure) showed slight improvement in performance, but her performance was still consistent with mild frontal/subcortical dysfunction. Although the initial screening of a brain magnetic resonance image (MRI) performed 15 months after the exposure was interpreted as being within normal limits, two subsequent blind reviews of the same scans identified multiple bilateral lesions in the basal ganglia, which were consistent with chronic CO exposure. We present this case as an example of the utility of MRI and neuropsychological examinations in detecting central nervous system dysfunction secondary to CO exposure

Probing Density Fluctuations using the FIRST Radio Survey

We use results of angular clustering measurements in 3000 sq. deg's of the FIRST radio survey to infer information on spatial clustering. Measurements are compared with CDM-model predictions. Clustering of FIRST sources with optical ID's in the APM catalog are also investigated. Finally, we outline a preliminary search for a weak lensing signal in the survey.Comment: 6 pages latex, 2 figures, to appear in Cosmology with the New Radio Surveys (Kluwer

Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

Power Spectrum of Velocity Fluctuations in the Universe

We investigate the power spectrum of velocity fluctuations in the universe, $V^2(k)$, starting from four different measures of velocity: (1) the power spectrum of velocity fluctuations from peculiar velocities of galaxies; (2) the rms peculiar velocity of galaxy clusters; (3) the power spectrum of velocity fluctuations from the power spectrum of density fluctuations in the galaxy distribution; (4) and the bulk velocity from peculiar velocities of galaxies. We show that measures (1) and (2) are not consistent with each other and either the power spectrum from peculiar velocities of galaxies is overestimated or the rms cluster peculiar velocity is underestimated. The amplitude of velocity fluctuations derived from the galaxy distribution (measure 3) depends on the parameter $\beta$. We estimate the parameter $\beta$ on the basis of measures (2) and (4). The power spectrum of velocity fluctuations from the galaxy distribution in the Stromlo-APM redshift survey is consistent with the observed rms cluster velocity and with the observed large-scale bulk flow when the parameter $\beta$ is in the range 0.4-0.5. In this case the value of the function $V(k)$ at wavelength $\lambda=120h^{-1}$Mpc is $\sim 350$ km s$^{-1}$ and the rms amplitude of the bulk flow at the radius $r=60h^{-1}$ Mpc is $\sim 340$ km s$^{-1}$. The velocity dispersion of galaxy systems originates mostly from the large-scale velocity fluctuations with wavelengths $\lambda >100h^{-1}$ Mpc.Comment: Astrophysical Journal, Vol. 493, in press: 23 pages, uses AAS Latex, and 14 separate postscript figure

Acupuncture for chronic neck pain: a pilot for a randomised controlled trial

Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain